神经元中NDR激酶的双重缺失导致神经退行性变。(A) 6周龄时NDR1 KO、NDR2 KO、NDR1/2 KO与对照小鼠的平均体重折线图。用普通的单因素方差分析或Kruskal-Wallis检验分析各时间点基因型组间体重差异。N = 20-30只/组。(B) NDR1 KO、NDR2 KO、NDR1/2 KO和对照组小鼠在6月龄前的生存概率图。N = 20-30只/组。(C, D) P20和12周龄NDR1/2 KO小鼠和对照小鼠脑切片Ctip2的免疫荧光染色。DAPI图像中白色箭头线表示皮层厚度，Ctip2图像中白色箭头线表示皮层上层I-IV层厚度。比例尺:200 μm。图表显示皮层厚度的量化，数据分析使用配对t检验。 n = 18 measurements from three mice/genotype. (E) Immunofluorescence staining of GFAP in brain slices of 12-wk-old NDR1/2 KO and control mice. White arrows show areas with increased GFAP signal in NDR1/2 KO mice. (F) Western blot analyses of GFAP levels in lysates from the cortex of 6-wk-old mice. GAPDH was used as a loading control. The graphs show quantifications of the GFAP bands normalized against the GAPDH levels, and the data were analyzed using an ordinary one-way ANOVA with Tukey’s post hoc test. n = 3–5 mice/group. (G) Immunofluorescence staining of GFAP and the microglial marker Iba1 in the CA1 area of the hippocampus. White arrows indicate cells expressing the above-mentioned markers. Scale bars: 50 µm. (H) Images from brain slices of 12-wk-old Thy1-YFP–expressing mice in the CA1 area of the hippocampus. White arrowed lines indicate the stratum radiatum, where CA1 neuron dendrites are visible in YFP. The graph shows quantification of the hippocampal thickness (marked by the dashed yellow line—including stratum oriens, the CA1 cell body area, stratum radiatum and stratum lacunosum-moleculare), and the data were analyzed using a paired t test. n = 18 measurements from three mice/genotype. (I) Images from brain slices of Thy1-YFP–expressing mice in the CA1 cell body layer. The white arrow shows membrane protrusions present in NDR1/2 knockout neurons. Credit:生命科学联盟(2022)。DOI: 10.26508 / lsa.202201712
